P1602: ACUTE EPISODES IN PATIENTS WITH CONGENITAL THROMBOTIC THROMBOCYTOPENIC PURPURA RECEIVING PROPHYLAXIS: POST HOC ANALYSIS OF A RETROSPECTIVE CHART REVIEW STUDY
Authors: Paul Coppo, Marie Scully, Johanna Kremer Hovinga, Erika Tarasco, Rosa Willock, Maria Jose Aragon, Parth Patwari, Linda T. Wang, Michael Cronin, Björn Mellgård, Olulade Ayodele, Ping Du
Journal: HemaSphere (2023)

Topic: 32. Platelet disorders Background: Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare, potentially life-threatening condition caused by an inherited deficiency of the metalloprotease ADAMTS13. Prophylaxis with plasma/factor VIII-based products to replenish ADAMTS13 has been commonly used to reduce cTTP-related adverse health outcomes, but limited evidence is available regarding long-term effects of prophylaxis. To address knowledge gaps in the health impacts of TTP and real-world disease management, a retrospective chart review study was conducted. Results of a post hoc analysis focusing on a subset of patients with cTTP who received regular, standard of care (SoC) prophylaxis are presented here. Aims: To describe characteristics of cTTP patients receiving regular SoC prophylaxis, real-world administration of SoC prophylaxis, and the frequency of acute TTP episodes in this population. Methods: An international, multi-center, retrospective chart review study of patients with confirmed cTTP or immune-mediated TTP diagnoses was conducted in 2021-2022. Patients were included in the chart review if they had any of the following events during 01/01/2009-31/12/2017: first TTP diagnosis, treatment for acute episode or subacute manifestation or TTP prevention, or TTP-related clinical event. Patient data from 01/01/2009 until death, loss to follow-up, enrollment in a clinical trial, or study end (31/12/2020) were collected. Ethics approval, and informed consent where applicable was obtained. This post hoc analysis included a subset of cTTP patients who had received regular SoC prophylaxis (plasma/factor VIII-based products administered at least once per month to up to 3 times per week). High-risk patients (aged >70 years [yrs], or with certain comorbidities: dementia, drug/alcohol dependence, HIV, cirrhosis or acute coronary syndrome), and prophylaxis during pregnancy in females aged ≥14 yrs were excluded from this analysis. The primary outcome was the incidence rate of acute TTP episodes defined by laboratory evidence of thrombocytopenia and microangiopathic hemolytic anemia (see Table). Results: Of the 78 patients with cTTP in the chart review, 25 patients (from France [n=17], the UK [n=4], Switzerland [n=2], Italy [n=1] and the US [n=1]) met the eligibility criteria for this post hoc analysis. Patients were predominantly female (68%), and median (interquartile range [IQR]) age at index was 23 (13-36) yrs. Median (IQR) duration of prophylaxis use was 6 (4-11) yrs, mostly with fresh frozen plasma (32/34 treatments). Most common reasons for starting prophylaxis were clinical symptomatology (40%) and TTP episode frequency (28%). Frequency of prophylaxis varied, with most treatments (82%) administered every 2-3 weeks. 18 treatments were interrupted/stopped because of complications, sub-optimal clinical benefits, or regimen switch. During the study period (164.4 person-yrs on prophylaxis), 4 patients experienced 9 acute TTP episodes (all requiring hospitalization; incidence rate: 0.055 per person-yr). Infection was the precipitating factor for 5 episodes (factors not reported for other episodes). Presenting symptoms and related hospitalizations are described in the Table. Summary/Conclusion: The incidence rate of acute episodes among cTTP patients who received regular SoC prophylaxis in this real-world study with a long-term follow-up period was 0.055 per person-yr on prophylaxis. The health impact was substantial as patients universally experienced hospitalizations with some requiring ICU stays during an acute episode, suggesting that current SoC prophylaxis may not provide sufficient protection against acute episodes.Keywords: Clinical data, ADAMTS13, Thrombotic thrombocytopenic purpura (TTP), Prophylaxis